Continued study of productive and abortive adenovirus-cell interactions should shed light on regulatory functions that may be crucial to the establishment and maintenance of the malignant state generally. The approaches focus on the modifying control exerted by adenovirus infection on cellular macromolecular synthesis and chromosome duplication. Human adenoviruses are viewed as convenient probes in tumor biology generally rather than as candidates for a major etiological role in naturally occurring human cancer. They are convenient and useful because (1) they are of human origin; (2) they encompass a spectrum of antigenically, biochemically, and structurally distinct types which differ in their oncogenic capacity. These differences reflect, in turn,the kind of infection a given adenovirus can establish in a given host or in cells derived from that host; (3) a vast amount of detailed knowledge has accumulated about the structure and replication of adenoviruses and, specifically, information flow from the viral genome to virus-specified transcriptional and translational products. Building on this rapidly evolving background of knowledge about the viruses themselves, we wish further to delineate those regulatory mechanisms operating in the normal cell cycle which are subject to modifications by adenovirus gene expression, or which themselves exert a controlloing effect on adenovirus replication. The experimental systems will involve the use of fresh serum and virus infection as activators of cell cycle progress in cells brought to arrest in G1 by various methods, the search for virus mutants unable to bring about this activation, and amino acid deprivation, especially of arginine, as a modifier of both viral replication and cellular macromolecular synthesis.